1. Field of the Invention
This invention relates to chemical analogs of the sweet glycosides, stevioside and rebaudioside A, which are themselves sweet and useful as sweeteners and which do not degrade under conditions of use to form physiologically undesirable steviol as do stevioside and rebaudioside A.
2. The Prior Art
The leaves of the Paraguayan shrub Stevia rebaudiana Bertoni have long been known to be sweet. Several sweet crystalline glycosides have been isolated from these leaves. The principal compound is named stevioside. The secondary compound differs from stevioside in the identity of its saccharide substituent and is known as rebaudioside A. These materials have the structures shown in general formulae I and II, respectively. ##STR1##
These compounds have been identified as possible sweeteners as they provide a relatively sucrose-like intense sweetness. A threshold question with these materials concerns their safety. In 1966, P. V. Vignais and coworkers reported the results of a study concerned with elucidation of the mode of action of the respiratory toxin, atractyligenin. Included in their study were several compounds of related structure including steviol (III), the aglycone of stevioside and rebaudioside A. ##STR2## Surprisingly, in cell mitochrondria, steviol was found to be an even more potent inhibitor of ATP synthetase then atractyligenin. (Biochim. Biophys. Acta, 118, 465-483 (1966)). In addition, steviol is reported to exhibit antiandrogenic effects (Dorfman, R. I., et al., Endocrinology, 67, 282-285 (1965)). Clearly, if stevioside and rebaudioside A were converted to steviol in vivo, significant toxicity may be expected. Recent results suggest the likelihood that both materials would be largely converted to steviol in vivo, and further that the steviol thus produced would subsequently be completely absorbed through the gastrointestinal tract wall. (R. Wingard, J. Dale, J. Brown, R. Hale, Experientia, 36, 519, (1980)) Thus, as a result of a combination of the Vignais and Wingard work, it may be concluded that, with widespread use, stevioside or rebaudioside A may be expected to exhibit significant acute toxicity. If, however, their metabolism to steviol could be prevented, that is if potently sweet analogs could be developed which were not degraded to steviol, safety for use in foods would be anticipated.
In copending U.S. patent application Ser. Nos. 272,799 now U.S. Pat. No. 4,353,889 and 272,798 of Grant E. DuBois, it is shown that the glucose attached to the C.sub.19 carboxyls of stevioside and rebaudioside A can be replaced with a polar nonglycosidic group while retaining sweetness.
Also in concurrently filed and now pending U.S. patent application Ser. No. 296,568 it is disclosed that sweet analogs of steviolmonoside can be formed.